Jie Gao, K. Mamouni, G. Kallifatidis, S. Panda, M. Thangaraju, B. L. Lokeshwar
{"title":"摘要5069:多香果中的三萜预防乳腺癌","authors":"Jie Gao, K. Mamouni, G. Kallifatidis, S. Panda, M. Thangaraju, B. L. Lokeshwar","doi":"10.1158/1538-7445.SABCS18-5069","DOIUrl":null,"url":null,"abstract":"Breast cancer ranks second as a lethal cancer in women. Although survival following initial diagnosis is ~ 100% in first five years, cancer progression and mortality is imminent in subsequent years. The slow progression to the lethal form of breast cancer has prompted development of multiple avenues to delay the progression, metastasis and mortality using potent prevention strategies, including the use of nutraceuticals. Oleanolic acid (OA) and ursolic acid (UA) are two triterpenoids found in edible plant parts-fruits and seeds with potent cancer preventive, and selective cytotoxic activities against multiple cancers including breast cancer. We conducted cytotoxic assays of the combination of OA and UA. We found the combination has enhanced efficacy as compared to OA or UA alone. The combination of OA and UA and UA alone caused cell death by increased autophagy but not apoptosis in both MCF7 and MB231 human breast cancer cells. Further analysis revealed increased autopagosomes and autophagic flux, inhibition of either process reduced cytotoxicity, indicating cytotoxic autophagy is the primary mechanism of their action. Therefore, a combination of OA and UA with conventional therapies could enhance their therapeutic efficacy while limiting systemic toxicities of existing therapies. Citation Format: Jie Gao, Kenza Mamouni, Georgios Kallifatidis, Siva Panda, Muthusamy Thangaraju, Bal L. Lokeshwar. Breast cancer prevention by triterpenoids from allspice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5069.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"13 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Abstract 5069: Breast cancer prevention by triterpenoids from allspice\",\"authors\":\"Jie Gao, K. Mamouni, G. Kallifatidis, S. Panda, M. Thangaraju, B. L. Lokeshwar\",\"doi\":\"10.1158/1538-7445.SABCS18-5069\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Breast cancer ranks second as a lethal cancer in women. Although survival following initial diagnosis is ~ 100% in first five years, cancer progression and mortality is imminent in subsequent years. The slow progression to the lethal form of breast cancer has prompted development of multiple avenues to delay the progression, metastasis and mortality using potent prevention strategies, including the use of nutraceuticals. Oleanolic acid (OA) and ursolic acid (UA) are two triterpenoids found in edible plant parts-fruits and seeds with potent cancer preventive, and selective cytotoxic activities against multiple cancers including breast cancer. We conducted cytotoxic assays of the combination of OA and UA. We found the combination has enhanced efficacy as compared to OA or UA alone. The combination of OA and UA and UA alone caused cell death by increased autophagy but not apoptosis in both MCF7 and MB231 human breast cancer cells. Further analysis revealed increased autopagosomes and autophagic flux, inhibition of either process reduced cytotoxicity, indicating cytotoxic autophagy is the primary mechanism of their action. Therefore, a combination of OA and UA with conventional therapies could enhance their therapeutic efficacy while limiting systemic toxicities of existing therapies. Citation Format: Jie Gao, Kenza Mamouni, Georgios Kallifatidis, Siva Panda, Muthusamy Thangaraju, Bal L. Lokeshwar. Breast cancer prevention by triterpenoids from allspice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5069.\",\"PeriodicalId\":20357,\"journal\":{\"name\":\"Prevention, Early Detection, and Interception\",\"volume\":\"13 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prevention, Early Detection, and Interception\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1158/1538-7445.SABCS18-5069\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prevention, Early Detection, and Interception","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1158/1538-7445.SABCS18-5069","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
乳腺癌在女性致命癌症中排名第二。虽然最初诊断后的5年生存率约为100%,但在随后的几年中,癌症进展和死亡率迫在眉睫。乳腺癌缓慢发展为致命形式,这促使人们开发了多种途径,通过使用有效的预防策略来延缓进展、转移和死亡率,包括使用营养保健品。齐墩果酸(OA)和熊果酸(UA)是存在于可食用植物果实和种子中的两种三萜,具有有效的癌症预防作用,并对包括乳腺癌在内的多种癌症具有选择性的细胞毒活性。我们对OA和UA联合用药进行了细胞毒性测定。我们发现联合用药比单独使用OA或UA更有效。在MCF7和MB231人乳腺癌细胞中,OA和UA联合使用和UA单独使用均通过增加细胞自噬而非凋亡导致细胞死亡。进一步分析显示,自噬体和自噬通量增加,抑制这两个过程均可降低细胞毒性,表明细胞毒性自噬是它们作用的主要机制。因此,OA和UA联合常规疗法可以提高其治疗效果,同时限制现有疗法的全身毒性。引用格式:Jie Gao, Kenza Mamouni, Georgios Kallifatidis, Siva Panda, Muthusamy Thangaraju, Bal L. Lokeshwar。多香果中三萜预防乳腺癌[摘要]。摘自:2019年美国癌症研究协会年会论文集;2019年3月29日至4月3日;亚特兰大,乔治亚州。费城(PA): AACR;癌症杂志,2019;79(13增刊):5069。
Abstract 5069: Breast cancer prevention by triterpenoids from allspice
Breast cancer ranks second as a lethal cancer in women. Although survival following initial diagnosis is ~ 100% in first five years, cancer progression and mortality is imminent in subsequent years. The slow progression to the lethal form of breast cancer has prompted development of multiple avenues to delay the progression, metastasis and mortality using potent prevention strategies, including the use of nutraceuticals. Oleanolic acid (OA) and ursolic acid (UA) are two triterpenoids found in edible plant parts-fruits and seeds with potent cancer preventive, and selective cytotoxic activities against multiple cancers including breast cancer. We conducted cytotoxic assays of the combination of OA and UA. We found the combination has enhanced efficacy as compared to OA or UA alone. The combination of OA and UA and UA alone caused cell death by increased autophagy but not apoptosis in both MCF7 and MB231 human breast cancer cells. Further analysis revealed increased autopagosomes and autophagic flux, inhibition of either process reduced cytotoxicity, indicating cytotoxic autophagy is the primary mechanism of their action. Therefore, a combination of OA and UA with conventional therapies could enhance their therapeutic efficacy while limiting systemic toxicities of existing therapies. Citation Format: Jie Gao, Kenza Mamouni, Georgios Kallifatidis, Siva Panda, Muthusamy Thangaraju, Bal L. Lokeshwar. Breast cancer prevention by triterpenoids from allspice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5069.